基于网络药理学及实验验证探讨黄连治疗龋齿的作用机制  

Mechanism of action of Coptis chinensis in the treatment of dental caries based on network pharmacology and experimental validation

作　　者：吕晓飞[1] 刘珍辉 蒋楠 崔晓彤 彭诚[1] Lyu Xiaofei;Liu Zhenhui;Jiang Nan;Cui Xiaotong;Peng Cheng(Department of Stomatology,The Second Hospital of Tianjin Medical University,Tianjin 300211,China;Department of Periodontology,Beijing Chongwen Stomatological Hospital,Beijing 100062,China;School and Hospital of Stomatology,Tianjin Medical University,Clinical School of Stomatology,Tianjin Medical University,Tianjin 300070,China)

机构地区：[1]天津医科大学第二医院口腔科,天津300211 [2]北京崇文口腔医院牙周病科,北京100062 [3]天津医科大学口腔医院,天津医科大学口腔临床学院,天津300070

出　　处：《国际生物医学工程杂志》2023年第4期321-328,共8页International Journal of Biomedical Engineering

摘　　要：目的探索使用网络药理学方法和动物实验研究黄连治疗龋齿的作用机制。方法通过中药系统药理学(TCMSP)数据库与分析平台筛选出黄连有效成分及其靶点,并通过GeneCards数据库在线检索疾病靶点。在Venny 2.1网站筛选出黄连和龋齿的交集靶点,并将交集靶点在线进行蛋白-蛋白相互作用分析和基因本体(GO)及京都基因与基因组百科全书(KEGG)富集分析。然后,使用Cytoscape制作"成分-靶点-通路"网络图。将大鼠随机分为模型组和黄连组,建立龋齿大鼠模型。模型组大鼠用浸有150 μl 0.9%氯化钠溶液小棉球反复涂擦大鼠磨牙各面5 min,黄连组大鼠将浸有黄连(5.8 mg黄连融入150 μl 0.9%氯化钠溶液)的小棉球反复涂擦大鼠磨牙各面5 min。2组大鼠每周处理1次,连续处理4周。对变异链球菌菌落数进行计数,并采用酶联免疫法检测血清丝氨酸/苏氨酸蛋白激酶1(AKT1)、JUN、白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、B淋巴细胞瘤-2(Bcl-2)蛋白表达。结果黄连中有11个有效成分,通过干预54个靶点,调节多个分子通路,从而治疗龋齿。槲皮素、小檗碱、黄藤素、小檗浸碱和四氢小檗碱等是核心成分,AKT1、JUN、IL-6、TNF、Bcl-2为核心靶点。GO分析显示,BP主要包括细胞因子活性、信号受体激活剂活性、信号受体调节剂活性、细胞因子受体结合和受体配体活性等;CC主要包括对脂多糖的反应、对细菌分子的反应、细胞对脂质的反应、炎症反应和细胞群体增殖负调控等;MF主要包括膜筏、膜微区、细胞外基质、外部封装结构和质膜蛋白复合物等。KEGG分析显示晚期糖基化终末产物-晚期糖基化终末产物受体(AGE-RAGE)、TNF、IL-17、Toll样受体、缺氧诱导因子-1(HIF-1)、丝裂原活化蛋白激酶(MAPK)、核因子-κB(NF-κB)、表皮生长因子受体(EGFR)、Janus激酶-信号转导子与转录激活子(JAK-STAT)、磷脂酰肌醇3-激酶-蛋白激酶B(PI3Objective To explore the mechanism of action of Coptis chinensis in the treatment of dental caries using a network pharmacology approach and animal experiments.Methods The active ingredients of C.chinensis and their targets were screened by the traditional Chinese medicine systems pharmacology(TCMSP)database and analysis platform,and the targets were searched online through the GeneCards database.The intersecting targets of C.chinensis and dental caries were screened at Venny 2.1,and the intersection targets were analyzed online for protein-protein interaction analysis and gene ontology(GO)and kyoto encyclopedia of genes and genomics(KEGG)enrichment.Then,Cytoscape was used to create a"component-target-pathway"network diagram.Rats were randomly divided into the model group and the C.chinensis group to establish a rat model of dental caries.Rats in the model group were repeatedly rubbed with a cotton ball soaked in 150μl of 0.9%NaCl solution for 5 min,and rats in the C.chinensis group were repeatedly rubbed with a cotton ball soaked in C.chinensis(5.8 mg of C.chinensis in 150μl of 0.9%NaCl solution)for 5 min.The two groups of rats were treated once a week for four consecutive weeks.The number of Streptococcus mutans colonies was counted,and serum serine/threonine protein kinase 1(AKT1),JUN,interleukin-6(IL-6),tumor necrosis factor(TNF),and B-cell lymphoma-2(Bcl-2)were detected by enzyme immunoassay.Results A total of 11 active ingredients in C.chinensis were found,which regulate multiple molecular pathways by intervening in 54 targets,thereby treating dental caries.Quercetin,berberine,flavodoxin,berberine infusion,and tetrahydroberberine were the core components,and AKT1,JUN,IL-6,TNF,and Bcl-2 were the core targets.GO analysis showed that BP mainly included cytokine activity,signaling receptor activator activity,signaling receptor modulator activity,cytokine receptor binding,and receptor ligand activity,etc.;and CC mainly included the response to lipopolysaccharides,the response to bacterial molecules,cellular re

关 键 词：黄连 龋齿 网络药理学 作用机制 实验验证 

分 类 号：R285[医药卫生—中药学]